The overall goal of this proposal is to develop an ultraminiature (350 [unreadable]m diameter) endoscopic imaging device with integrated laser therapy capabilities for microsurgical applications inside the body. The specific goal of this proposal is to develop a device for safe and effective treatment of twin-twin transfusion syndrome (TTTS). TTTS is a complication of monochorionic pregnancies that occurs in approximately 3000 pregnancies/year in the United States. In TTTS, an imbalance of blood flow across placental arteriovenous anastomoses deprives the donor twin of blood, while the recipient twin becomes hypervolemic. When left untreated, fetal mortality is very high, up to 90% in some studies. Laser ablation of all of the communicating vessels in utero is an effective treatment for TTTS. However, current fetoscopy technology used to guide this procedure is not adequate for this application. The relatively large size of operative fetoscopes (2-3 mm diameter) leads to unacceptably high complication rates, including iatrogenic preterm premature rupture of membranes and in utero fetal demise. Adverse perinatal outcomes are also common, due in part to the poor image quality of modern fetosocopes, which causes many anatomoses to be missed. In this proposal we will overcome the limitations of current TTTS therapy devices by developing a much smaller microsurgical endoscope that provides more informative images with better image quality. This advance will be enabled by a new technology, termed spectrally encoded endoscopy (SEE) that uses wavelength division multiplexing to obtain high-resolution images through a single optical fiber. Our group has previously demonstrated endoscopic two- and three-dimensional video-rate imaging using a 350 [unreadable]m diameter, monochromatic version of this device in vivo. In the proposed research, we will extend the SEE system and probe for color differentiation of arterial and venous placental vessels and will add Doppler imaging to quantify blood flow. Additionally, we will incorporate therapeutic laser delivery through the same probe without increasing its size. The total diameter of our device will be 350 [unreadable]m, small enough to be introduced into the amniotic cavity through an amniocentesis needle (22-gauge), which should provide a 10-fold reduction in complication rate. The effectiveness and safety of our SEE system and probe will be compared with that of commercially available fetal laser therapy systems in a study of 10 pregnant ewes. While the immediate focus of the proposed research is placental vascular coagulation, this new technology holds promise as a platform technology for a wide variety of minimally invasive procedures, especially those where probe size is critical. In this proposal, we will develop an ultraminiature (350 [unreadable]m diameter) endoscopic imaging device with integrated laser therapy capabilities for microsurgical applications inside the body. The specific goal of this research is to create a device for safe and effective treatment of twin-twin transfusion syndrome (TTTS), a severe complication of twin pregnancies that carries a high fetal mortality rate. We will accomplish our aims by advancing a new technology, termed spectrally encoded endoscopy (SEE) that uses wavelength division multiplexing to obtain high-resolution images through a single optical fiber. In addition to treatment of TTTS, this device can be used for endoscopically-guided therapy in other applications where ultraminiature instrumentation is critical for tissue access and patient safety. [unreadable] [unreadable] [unreadable]